There has been considerable recent interest in the incorporation of nanoscale components in lab-on-a-chip fluidic devices. This interest owes its origin to several advantages (and differences that may be advantageously leveraged) in moving from the micron scale to the nanoscale. These differences include, for example, double-layer overlap (DLO) and its effect on electro-osmosis and charge permselectivity, localized enhancement of electric fields, higher surface to volume ratios, confinement effects on large synthetic and biopolymers, and the emerging importance of entropic effects. See, e.g., Yuan et al., Electrophoresis 2007, 28, 595-610; Schoch et al., Rev. Mod. Phys. 2008, 80, 839-883; and Kovarik et al., Anal. Chem. 2009, 81, 7133-7140. Historic examples of nanoscale devices include the use of porous media and gels in chromatographic separations and filtration membranes with nanoscale pores. See, e.g., Lerman et al., Biopolymers 1982, 21, 995-997; and Tong et al., M. Nano Lett. 2004, 4, 283-287. Recent efforts, however, have been focused on engineering geometrically well-defined conduits for fluid and analyte transport and seamlessly integrating them into devices. See, e.g., Volkmuth et al., Nature 1992, 358, 600-602; and Striemer et al., Nature 2007, 445, 749-753. The advantage of such regular structures is the relative simplicity of pressure and field gradients, fluid flow, and molecular motion contained within, in contrast to these properties in more tortuous networks. The capability to define, characterize, and easily model these systems can allow a better understandings of separation mechanisms and single molecule physics, for example. See, e.g., Volkmuth et al., Nature 1992, 358, 600-602; Reisner et al., Phys. Rev. Lett. 2005, 94, 196101; and Salieb-Beugelaar et al., Lab Chip 2009, 9, 2508-2523.
A number of fabrication tools have been brought to bear on the challenge of fabricating nanochannels. The methods suitable for nanochannel fabrication have been extensively reviewed. See, e.g., Douville et al., Anal. Bioanal. Chem. 2008, 391, 2395-2409; Mijatovic et al., A. Lab Chip 2005, 5, 492-500; Perry et al., Microfluid. Nanofluid. 2006, 2, 185-193; and Abgrall et al., Anal. Chem. 2008, 80, 2326-2341. Photolithography has been used to fabricate “nanoslits”—features with widths defined by the resolution limits of photolithography (i.e. usually several hundred nm to microns) and nanometer-scale depths defined by short duration wet or dry etching techniques. See, e.g., Cross et al., J. Appl. Phys. 2007, 102, 024701; Balducci et al., Macromolecules 2006, 39, 6273-6281; and Salieb-Beugelaar et al., Nano Lett. 2008, 8, 1785-1790. Nanoimprint lithography has been shown capable of producing nanofluidic channels that are as small as 10 nm wide. See, e.g., Cao et al., Appl. Phys. Lett. 2002, 81, 174-176. Electron beam lithography (EBL) has been used to pattern nanochannels for use in DNA extension studies with dimensions as small as 50 nm. See, e.g., Reisner et al., Phys. Rev. Lett. 2007, 99, 058302. Single DNA molecules have also been studied in focused ion beam (FIB) milled nanochannels on the order of 100 nm. See, e.g., Campbell et al., Lab Chip 2004, 4, 225-229; and Riehn et al., Proc. Natl. Acad. Sci, USA 2005, 102, 10012-10016. Various templating and molding strategies have also been used to generate nanochannels for nanofluidic studies in the 50-100 nm range. See, e.g., Fan et al., Nano Lett. 2005, 5, 1633-1637; and Huh et al., S. Nat. Mater. 2007, 6, 424-428. Ultimate dimensions for templating strategies have alleged to be able to extend below 10 nm, although channels this small have not been demonstrated as platforms in fluidic experiments. See, e.g., Nikoobakht, B., Chem. Mater. 2009, 21, 27-32.